Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release

Etienne Lonchamp, Jean Luc Dupont, Laetitia Wioland, Raphael Jean Courjaret, Corinne Mbebi-Liegeois, Emmanuel Jover, Frédéric Doussau, Michel R. Popoff, Jean Louis Bossu, Jean de Barry, Bernard Poulain

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Epsilon toxin (ET) produced by C. perfringens types B and D is a highly potent pore-forming toxin. ET-intoxicated animals express severe neurological disorders that are thought to result from the formation of vasogenic brain edemas and indirect neuronal excitotoxicity. The cerebellum is a predilection site for ET damage. ET has been proposed to bind to glial cells such as astrocytes and oligodendrocytes. However, the possibility that ET binds and attacks the eurons remains an open question. Using specific anti-ET mouse polyclonal antibodies and mouse brain slices preincubated with ET, we found that several brain structures were labeled, the cerebellum being a prominent one. In cerebellar slices, we analyzed the costaining of ET with specific cell markers, and found that ET binds to the cell body of granule cells, oligodendrocytes, but not astrocytes or nerve endings. Identification of granule cells as neuronal ET targets was confirmed by the observation that ET induced intracellular Ca2+ rises and glutamate release in primary cultures of granule cells. In cultured cerebellar slices, whole cell patch-clamp recordings of synaptic currents in Purkinje cells revealed that ET greatly stimulates both spontaneous excitatory and inhibitory activities. However, pharmacological dissection of these effects indicated that they were only a result of an increased granule cell firing activity and did not involve a direct action of the toxin on glutamatergic nerve terminals or inhibitory interneurons. Patch-clamp recordings of granule cell somata showed that ET causes a decrease in neuronal membrane resistance associated with pore-opening and depolarization of the neuronal membrane, which subsequently lead to the firing of the neuronal network and stimulation of glutamate release. This work demonstrates that a subset of neurons can be directly targeted by ET, suggesting that part of ET-induced neuronal damage observed in neuronal tissue is due to a direct effect of ET on neurons.

Original languageEnglish
Article numbere13046
Pages (from-to)1-15
Number of pages15
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 1 Nov 2010
Externally publishedYes

Fingerprint

Clostridium perfringens
cerebellum
glutamates
Cerebellum
Glutamic Acid
granules
Brain
toxins
Clamping devices
Neurons
mice
Membranes
Dissection
Oligodendroglia
Depolarization
Carisoprodol
cells
Astrocytes
Animals
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. / Lonchamp, Etienne; Dupont, Jean Luc; Wioland, Laetitia; Courjaret, Raphael Jean; Mbebi-Liegeois, Corinne; Jover, Emmanuel; Doussau, Frédéric; Popoff, Michel R.; Bossu, Jean Louis; de Barry, Jean; Poulain, Bernard.

In: PLoS One, Vol. 5, No. 9, e13046, 01.11.2010, p. 1-15.

Research output: Contribution to journalArticle

Lonchamp, E, Dupont, JL, Wioland, L, Courjaret, RJ, Mbebi-Liegeois, C, Jover, E, Doussau, F, Popoff, MR, Bossu, JL, de Barry, J & Poulain, B 2010, 'Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release', PLoS One, vol. 5, no. 9, e13046, pp. 1-15. https://doi.org/10.1371/journal.pone.0013046
Lonchamp, Etienne ; Dupont, Jean Luc ; Wioland, Laetitia ; Courjaret, Raphael Jean ; Mbebi-Liegeois, Corinne ; Jover, Emmanuel ; Doussau, Frédéric ; Popoff, Michel R. ; Bossu, Jean Louis ; de Barry, Jean ; Poulain, Bernard. / Clostridium perfringens epsilon toxin targets granule cells in the mouse cerebellum and stimulates glutamate release. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-15.
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